长期生长激素治疗可提高努南综合征患儿的成年身高，无论其蛋白酪氨酸磷酸酶非受体11型有无突变。

Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11.

作者信息

Noordam C, Peer P G M, Francois I, De Schepper J, van den Burgt I, Otten B J

机构信息

Department of Metabolic and Endocrine Diseases 833, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.

出版信息

Eur J Endocrinol. 2008 Sep;159(3):203-8. doi: 10.1530/EJE-08-0413. Epub 2008 Jun 18.

DOI:10.1530/EJE-08-0413

PMID:18562489

Abstract

CONTEXT

Noonan syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. Short-term effect of GH therapy in NS is beneficial, reports on the effect on adult height are scarce.

OBJECTIVE

To determine the effect of long-term GH therapy in children with NS.

DESIGN

Twenty-nine children with NS were treated with GH until final height was reached.

SETTING

Hospital endocrinology departments.

PATIENTS

Children with the clinical diagnosis of NS, with mean age at the start of therapy of 11.0 years, 22 out of 27 tested children had a mutation in the protein tyrosine phosphatase, non-receptor-type 11 gene (PTPN11 gene). Interventions GH was administered subcutaneously at 0.05 mg/kg per day until growth velocity was 1 cm/6 months.

MAIN OUTCOME MEASURE

Linear growth (height) was measured at 3-month intervals in the first year and at 6-month intervals thereafter until final height.

RESULTS

At the start of treatment, median height SDS (H-SDS) was -2.8 (-4.1 to -1.8) and 0.0 (-1.4 to +1.2), based on national and Noonan standards respectively. GH therapy lasted for 3.0-10.3 years (median, 6.4), producing mean gains in H-SDS of +1.3 (+0.2 to +2.7) and +1.3 (-0.6 to +2.4), based on national and Noonan standards respectively. In 22 children with a mutation in PTPN11 mean gain in H-SDS for National standards was +1.3, not different from the mean gain in the five children without a mutation in PTPN11+1.3 (P=0.98).

CONCLUSION

Long-term GH treatment in NS leads to attainment of adult height within the normal range in most patients.

摘要

背景

努南综合征（NS）的特征为身材矮小、典型的面部畸形和先天性心脏缺陷。生长激素（GH）治疗对NS的短期效果是有益的，但关于其对成人身高影响的报道较少。

目的

确定长期GH治疗对NS患儿的影响。

设计

29例NS患儿接受GH治疗直至达到最终身高。

地点

医院内分泌科。

患者

临床诊断为NS的患儿，治疗开始时平均年龄为11.0岁，27例接受检测的患儿中有22例在蛋白酪氨酸磷酸酶非受体11型基因（PTPN11基因）存在突变。干预措施：GH以每日0.05mg/kg的剂量皮下注射，直至生长速度为1cm/6个月。

主要观察指标

在治疗的第一年每3个月测量一次线性生长（身高），此后每6个月测量一次，直至达到最终身高。

结果

治疗开始时，根据国家和努南标准，身高标准差（H-SDS）中位数分别为-2.8（-4.1至-1.8）和0.0（-1.4至+1.2）。GH治疗持续3.0至10.3年（中位数为6.4年），根据国家和努南标准，H-SDS的平均增加量分别为+1.3（+0.2至+2.7）和+1.3（-0.6至+2.4）。在22例PTPN11基因发生突变的患儿中，按照国家标准H-SDS的平均增加量为+1.3，与5例PTPN11基因未发生突变患儿的平均增加量+1.3无差异（P=0.98）。